Quantitative aspects of the interaction of bile acids with human serum albumin.

Fluorescence behavior of ethidium bromide in homogeneous solvents and in presence of bile acid hosts

“…It is indeed well known that in vitro binding of BAs to exogenous substrates depends on the specific binding nature [39] and, therefore, the binding constant values in different cases may vary over huge range depending on the substrate as well as the receptor. Nevertheless, the binding constant values measured from the fluorescence based study on the interaction of BAs with human serum albumin (10 3 -10 4 M −1 ) [40] is in good agreement with the values calculated from the present study. Interestingly, the binding constants of EB with the BAs calculated here is almost an order of magnitude higher than the corresponding values for an organic charge transfer system reported earlier [20].…”

Natural Bile Acids and Synthetic Analogues Modulate Large Conductance Ca2+-activated K+ (BKCa) Channel Activity in Smooth Muscle Cells

“…Under physiological conditions, systemically circulating levels of bile acids in fasting humans are usually 2-10 M, which is sixfold lower than those in the portal circulation (Scharschmidt, 1982;Ceryak et al, 1993;Güldütuna et al, 1993). These circulating bile acids are Ͼ95% bound to albumin (Burke et al, 1971;Roda et al, 1982). Thus, one could speculate that circulating low concentrations of free bile acids would not have a major role in increasing BK Ca channel activity and relaxing systemic arterial smooth muscle under normal physiological conditions.…”

“…Protein Site(s): An ion channel protein-bile acid direct interaction is quite possible since there is wide precedence for the interaction of polypeptides or proteins and bile acid monomers (Roda et al, 1990), which, as discussed below, are most likely the molecular form responsible for increasing BK Ca channel activity. The dissociation constants (K d s) for bile acid binding to selective affinity sites on circulating plasma proteins range from 2-5 M (lithocholic acid binding to albumin) to 2,500 M (cholic acid binding to delipidated human lipoprotein) (Roda et al, 1982;Ceryak et al, 1993). A similar range of K d s is found for the binding of bile acids to a variety of cytosolic binding proteins: from 0.5 M (lithocholic acid binding to the Ya class of glutathione S-transferases) to 1,000 M (cholic acid and derivatives binding to fatty acid binding protein) (reviewed in Stolz et al, 1989).…”

“…All of these affinity constants are within the range of concentrations reported here for bile acids to effectively enhance BK Ca channel activity (3-1,000 M; Table I, legend). In addition, the high affinity, specific binding of bile acids to albumin correlates with the hydrophobicity of bile acid monomers, with the K d for lithocholic acid (5 M) being smaller than that for deoxycholic acid (25 M) and smaller still than that for cholic acid (333 M; Roda et al, 1982;Picó et al, 1989;Ceryak et al, 1993). A similar order and range of affinities is found for the binding of these bile acids to the nuclear farnesoid X receptor (Parks et al, 1999).…”

Bile Acids, Liver Cirrhosis, and Extrahepatic Vascular Dysfunction

“…In contrast, in liver cirrhosis, the total bile acid concentration in the peripheral venous blood corresponds to the concentration in the portal vein or may even be higher, partly due to shunting ( Ohkubo et al, 1984 ). In blood, bile acids are tightly bound to serum albumin and lipoproteins ( Rudman and Kendall, 1957 ; Kramer et al, 1979 ; Roda et al, 1982 ; Ceryak et al, 1993 ), hydrophobic bile acids predominantly to albumin and hydrophilic bile acids also to lipoprotein particles, especially HDL and LDL.…”